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Biography
Sabine Tötemeyer obtained a Diplom in Biology (roughly equivalent to MSc) in Microbiology, Biochemistry and Plant Physiology from the University of Osnabrück in Germany. She obtained a PhD from the University of Aberdeen in 1997. She then spent two years as a postdoctoral research associate at the Christian de Duve Institute for Medical Sciences, Université Catholique de Louvain, Brussels, Belgium. This was followed by six years of research in the Cell Biology of Infection Group at the Centre for Veterinary Science, Cambridge Veterinary School, University of Cambridge. She joined the newly formed School of Veterinary Medicine and Science in 2006. She is involved in module convening of the Lymphoreticular Cell Biology (LCB) module in Year 1 & 4 and areas of teaching include cell biology, microbiology, host pathogen interactions, innate immunity, antibody based and molecular diagnostics ass well as Personal and Professional Skills (PPS) and communications skills. Her research interest include the Role of Toll-like receptors (TLRs) in host-bacteria interaction sand the development of complex epithelial tissue culture models. Current research focusses on undeerratndign host pathogen interactison in footrot in sheep and listeriosis in cattle. She also has an interest in educational research with an emphasis on assessment and feedback, 1st year experience and student selection/admission.
Expertise Summary
Sabine Tötemeyer is a Lecturer in Cellular Microbiology, a convener for the year 1 module D11LCB and co-convener for the year 4 module D14LCB.
Teaching Summary
I am involved in convening the Lymphoreticular Cell Biology (LCB) modules in year 1 and 4 (D11LCB & D14LCB) covering cell biology, immunology and heammatology. I contribute to other modules… read more
Research Summary
My main interest is in the host-bacterial interactions and the development of complex in vitro tissue culture systems
1. Understanding inflammatory processes in ovine footrot
In England more than 95% of sheep flocks have footrot, with an estimated cost to the UK sheep industry of £24-84M per annum. Footrot is caused by bacteria that invade the skin of the foot, and cause pain and separation of the horn from the hoof.
Antibiotic injection early in disease leads to recovery within a few days. In the long term however, it would be preferable to instead use vaccination (currently vaccination is part of a 5 point management plan, rather than a single preventative measure), helping to reduce our reliance on and use of antibiotics.
By studying the local immune defences in the sheep foot and how the bacteria causing footrot are recognised by the immune system, in addition to a complementary molecular analysis of the primary pathogen associated with disease, researchers hope to explain better how the clinical signs of footrot are caused and how the immune system contributes to this. The study will help to inform new approaches to disease management and ultimately disease prevention.
Our projects are funded by BBSRC's Animal Health Research Club (ARC), Capes Brazil & Tertiary Education Trust Fund (tetfund) Nigeria
2. Listeriosis in cattle
The intracellular pathogen Listeria monocytogenes is of major importance to global food security and of public health relevance. L. monocytogenes is foodborne pathogen but also impacts on the reproductive performance of beef and dairy cattle. Infection in ruminants manifests as keratoconjunctivitis or bacteraemia, which can lead to abortion or meningitis, hence causing production losses due to calf losses through abortion and extra veterinary bills, whilst delaying conception, compromising herd health and reducing milk yield after abortion leading to an average cost of £630 per abortion in a dairy herd.
Our research focuses on host pathogen interactions in conjunctival and reproductive tissues using tissue and organ culture models.
Other research interests:
- Role of Toll-like receptors (TLRs) in host-bacteria interactions
The innate immune system is of crucial importance for achieving homeostasis in the intestinal environment and the host response to pathogens. Toll-like receptors (TLRs) are a family of membrane receptors that recognize a wide range of pathogen associated molecular patterns (PAMPs). We are studying the modulation of TLR expression and cytokine production due to interactions with probiotics and/or pathogens. 1. Interactions of epithelial intestinal cells with commensals and pathogens (incl Clostridium difficile, Salmonella, Vibrio etc) 2. Interaction of bovine caruncular epithelia cells with abortifacient pathogens Leptospira 3. Effect of probiotics on weaning stress in pigs
- Development of complex epithelial tissue culture models
In research, due to increasing ethical awareness and technical developments, there is an increased need for models that mimic organs and tissues. To achieve better likeness to in vivo situation for the study of disease processes and host we are using and developing complex tissue culture systems 1. bacterial interactions in the intestinal tract, we are developing 3D tissue culture using rotary systems and reduced oxygen concentration. 2. Air interface culture systems 3. Organoid models using feeder cells to sustain tissue biopsies/necropsies
My areas of interest include 1. Assessment and feedback 2. First year experience (graduate students, international students) 3. Student selection/admission
Past Research
(1) Role of Toll like receptors in Salmonella infection
My work involves the analysis of bacterial growth and the host immune response mediated by toll like receptors (TLRs) during Salmonella infection in vivo (mouse typhoid model) and in vitro (bone marrow derived macrophages (BMDM) & cell lines). I have investigated the mRNA expression of TLR2, TLR4, and MD2 in spleens and livers of C3H/HeN mice (carrying wild-type TLR4) and C3H/HeJ mice (carrying mutated TLR4) in response to Salmonella infection. During Salmonella infections, TLR4 is activated, leading to increased TLR2 and decreased TLR4 expression (Tötemeyer et al., 2003). I also characterized the expression of a wide range of TLRs, TLR associated molecules and inflammatory mediators in C57/BL6 mice (Tötemeyer et al., 2005). In BMDM in response to Salmonella infection, production of nitric oxide (NO) is fully dependent on the activation of TLR4, while the production of TNFS is only partially TLR4 dependent (Royle et al., 2003). TLR4 plays an important role in SipB independent Salmonella induced cell death via the adapter molecules Trif and Tram (Cook, Tötemeyer et al. 2007). Stimulation of bone marrow derived macrophages with IFNg results in the production of NO in response to the bacterial cell wall component peptidoglycan in a TLR independent, Nod dependent way (Tötemeyer et al 2006).
(2) Adaptation of bacteria to intracellular environment
Array technology was used to investigating how Salmonella adapts to the intracellular macrophage environment. Infection of BMDMs from phox-/- and TLR4-/- mice followed by isolation of bacterial RNA allowed to determine the changes occurring in Salmonella gene expression using microarrays. I identified known genes required for the adaptation to an environment containing reactive oxygen species as well as genes of unknown function that might also be critical for S. typhimurium survival within macrophages (Wright, Tötemeyer et al, in preparation).